Multimodal Imaging of Nanovaccine Carriers Targeted to Human Dendritic Cells

Cruz, Luis J.; Tacken, Paul J.; Bonetto, F.; Buschow, Sonja I.; Croes, H.J.E.; Wijers, Mietske; Vries, I. Jolanda M. de; Figdor, Carl G.

doi:10.1021/mp100356k

Cited by 73 publications

(59 citation statements)

References 40 publications

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“…De Vries et al have shown that in vivo magnetic resonance tracking of MNS labeled dendritic cells is feasible in humans in conjunction with detailed anatomical information in melanoma patients. In contrast to scintigraphic imaging, MRI allowed assessment of the accuracy of dendritic cell delivery and of inter- and intranodal cell migration patterns [139–143]. Recently, Bulte et al evaluated the long-term clinical tracking of MNS labeled stem cells after intracerebroventricular transplantation in an 18-month-old patient with global cerebral ischemia [144].…”

Section: Mns For Diagnostic Imaging Of Cancermentioning

confidence: 99%

Theranostic Magnetic Nanostructures (MNS) for Cancer

Nandwana

Chu³

et al. 2015

Cancer Treatment and Research

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Despite the complexities of cancer, remarkable diagnostic and therapeutic advances have been made during the past decade, which include improved genetic, molecular, and nanoscale understanding of the disease. Physical science and engineering, and nanotechnology in particular, have contributed to these developments through out-of-the-box ideas and initiatives from perspectives that are far removed from classical biological and medicinal aspects of cancer. Nanostructures, in particular, are being effectively utilized in sensing/diagnostics of cancer while nanoscale carriers are able to deliver therapeutic cargo for timed and controlled release at localized tumor sites. Magnetic nanostructures (MNS) have especially attracted considerable attention of researchers to address cancer diagnostics and therapy. A significant part of the promise of MNS lies in their potential for “theranostic” applications, wherein diagnostics makes use of the enhanced localized contrast in magnetic resonance imaging (MRI) while therapy leverages the ability of MNS to heat under external radio frequency (RF) field for thermal therapy or use of thermal activation for release of therapy cargo. In this chapter, we report some of the key developments in recent years in regard to MNS as potential theranostic carriers. We describe that the r2 relaxivity of MNS can be maximized by allowing water (proton) diffusion in the vicinity of MNS by polyethylene glycol (PEG) anchoring, which also facilitates excellent fluidic stability in various media and extended in vivo circulation while maintaining high r2 values needed for T2-weighted MRI contrast. Further, the specific absorption rate (SAR) required for thermal activation of MNS can be tailored by controlling composition and size of MNS. Together, emerging MNS show considerable promise to realize theranostic potential. We discuss that properly functionalized MNS can be designed to provide remarkable in vivo stability and accompanying pharmacokinetics exhibit organ localization that can be tailored for specific applications. In this context, even iron-based MNS show extended circulation as well as diverse organ accumulation beyond liver, which otherwise renders MNS potentially toxic to liver function. We believe that MNS, including those based on iron oxides, have entered a renaissance era where intelligent synthesis, functionalization, stabilization, and targeting provide ample evidence for applications in localized cancer theranostics.

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Section: Mns For Diagnostic Imaging Of Cancermentioning

confidence: 99%

Theranostic Magnetic Nanostructures (MNS) for Cancer

Nandwana

Chu³

et al. 2015

Cancer Treatment and Research

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“…17 Limited studies have explored the use of carbohydrate-functionalized vaccine carriers as targeting vehicles, with most studies using antibodies as ligands. 18 This study outlines a novel approach to target the mannose receptor (CD206) and CIRE (CD209) on murine DCs by mimicking carbohydrate moieties found on the surface of pathogens. 19 Polyanhydride nanoparticle surfaces were functionalized with dimannose in order to study specific interactions with both CLRs known to recognize mannose residues.…”

Section: Abstract: Polyanhydrides Nanoparticles Carbohydrates Dendmentioning

confidence: 99%

Mannose-Functionalized “Pathogen-like” Polyanhydride Nanoparticles Target C-Type Lectin Receptors on Dendritic Cells

et al. 2011

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Targeting pathogen recognition receptors on dendritic cells (DCs) offers the advantage of triggering specific signaling pathways to induce a tailored and robust immune response. In this work, we describe a novel approach to targeted antigen delivery by decorating the surface of polyanhydride nanoparticles with specific carbohydrates to provide "pathogen-like" properties that ensure nanoparticles engage C-type lectin receptors on DCs. The surface of polyanhydride nanoparticles was functionalized by covalent linkage of dimannose and lactose residues using an amine-carboxylic acid coupling reaction. Coculture of functionalized nanoparticles with bone marrow-derived DCs significantly increased cell surface expression of MHC II, the T cell costimulatory molecules CD86 and CD40, the C-type lectin receptor CIRE and the mannose receptor CD206 over the nonfunctionalized nanoparticles. Both nonfunctionalized and functionalized nanoparticles were efficiently internalized by DCs, indicating that internalization of functionalized nanoparticles was necessary but not sufficient to activate DCs. Blocking the mannose and CIRE receptors prior to the addition of functionalized nanoparticles to the culture inhibited the increased surface expression of MHC II, CD40 and CD86. Together, these data indicate that engagement of CIRE and the mannose receptor is a key mechanism by which functionalized nanoparticles activate DCs. These studies provide valuable insights into the rational design of targeted nanovaccine platforms to induce robust immune responses and improve vaccine efficacy. The use of vaccine adjuvants to activate the innate immune system is crucial to vaccine effectiveness. 1 Adjuvants can be used to enhance the efficacy of single dose vaccines and reduce the required antigen dose. The use of biodegradable polymer nanoparticles as vaccine delivery vehicles allows for effective delivery of payloads by parental or mucosal administration by protecting the antigen from harsh physiological conditions and enabling transport across biological barriers (e.g., mucus membranes). 2 Polyanhydride nanoparticles have shown excellent potential as vaccine carriers. 3À6 Encapsulation of protein antigens into polyanhydride particles stabilizes them and provides sustained azntigen release; 4,7 these particles also enhance the immune response by acting as an adjuvant. 3 Dendritic cells (DCs) are antigen presenting cells (APCs) that play a major role in connecting the innate and adaptive immune systems, a key step to inducing protective immunity. 8 DCs can sense and internalize antigen by a variety of mechanisms that trigger DC maturation and direct further interactions with other immune cells, including naive T cells. 1,9,10 Pattern recognition receptors (PRRs) on DCs detect the presence of a potential threat by interacting with pathogen-associated molecular patterns (PAMPs). 10,11 In particular, C-type lectin receptors (CLRs) are PRRs with highly conserved carbohydrate-recognition domains that bind sugar moieties (e.g., mannose, fuco...

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“…In diagnostic, prophylactic and therapeutic approaches, nanoparticles have been used for imaging purposes [9], and/or as drug carrying adjuvant to enhance virucidal properties [10]. Virucidal nanoparticles and drug delivery models have been used mainly for the fighting Human immunodeficiency virus (HIV), hepatitis (type A, B, C and E) and herpes simplex virus (HSV-1&2).…”

Section: Introductionmentioning

confidence: 99%

Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections

Yadavalli

Shukla

2017

Nanomedicine: Nanotechnology, Biology and Medicine

157

111

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Nanotechnology is increasingly playing important roles in various fields including virology. The emerging use of metal or metal oxide nanoparticles in virus targeting formulations shows the promise of improved diagnostic or therapeutic ability of the agents while uniquely enhancing the prospects of targeted drug delivery. Although a number of nanoparticles varying in composition, size, shape, and surface properties have been approved for human use, the candidates being tested or approved for clinical diagnosis and treatment of viral infections are relatively less in number. Challenges remain in this domain due to a lack of essential knowledge regarding the in vivo comportment of nanoparticles during viral infections. This review provides a broad overview of recent advances in diagnostic, prophylactic and therapeutic applications of metal and metal oxide nanoparticles in Human Immunodeficiency Virus, Hepatitis virus, influenza virus and Herpes virus infections. Types of nanoparticles commonly used and their broad applications have been explained in this review.

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Multimodal Imaging of Nanovaccine Carriers Targeted to Human Dendritic Cells

Cited by 73 publications

References 40 publications

Theranostic Magnetic Nanostructures (MNS) for Cancer

Theranostic Magnetic Nanostructures (MNS) for Cancer

Mannose-Functionalized “Pathogen-like” Polyanhydride Nanoparticles Target C-Type Lectin Receptors on Dendritic Cells

Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections

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